High dose ifosfamide for patients with stage IV non small cell lung cancer: phase II trial from the Group francais de pneumo-cancerologie (GFPC)

Purpose: To assess the toxicity and efficacy of high dose ifosfamide in sta ge IV NSCLC. Methods: In a previous trial, we have determined maximum toler ated dose Sor 3-days ifosfamide treatment by 3-weeks schedule as 9 g/m(2) a ccording to hematologic tolerance. We therefore set up a phase Il to study the toxicity and efficacy of this schedule in chemotherapy naive metastatic NSCLC. Ifosfamide (+ mesna 1 g/m(2)) was administered by a two hour infusi on (3 g/m(2)) for three days every three weeks. Patients received three mes na bolus infusions (1 g/m(2)) at 4, 8 and 12 hours after the end of ifosfam ide infusion. Antitumoral efficacy was performed after 2 cycles and treatme nt could be pursued for responding patients until disease progression. From september 1995 to January 1997, 31 patients have been included in this stu dy. Median age was 60,7 years +/- 1,33 (41-70) for 27 males and 4 females. Patients (pts) presented metastases in lung for 10 pts, bone for 10 pts, li ver for 6 pts, adrenal for 4 pts and multiorgan metastatic localisation for 1 patient. Seven patients were unassessable: 1 lost for follow-up, 1 sudde n death, 5 treatment interruptions before evaluation time and 3 toxic death s (9,6%). Toxicity: neutropenia grade 4 (10 pts and 1 death), cardiotoxicit y grade 4 (1 pt) and 2 deaths following neurotoxicity grade 4. We achieve 4 partial responses (13%, 95CI: 3,6-29,8), 10 progressive diseases (32,3%, 3 5Cl: 16,7-51,4) and 10 stabilisations (32,3%, 35Cl: 16;7-51,4). Median resp onse duration was 91 day +/- 55d. Median survival was 9,3 months, e.g. 280 days (8-863). Overall survival at one year is 48%. Conclusion: This modalit y of high dose ifosfamide is as effective as standard monotherapy schedules in stage IV NSCLC. Unexpected toxicities particularly hematological ones c ould be due to a short duration of fractionated treatment. Results in term of survival leads us to further evaluate ifosfamide monotherapy treatment o n a 5-day schedule basis.